One great advantage of power-law representations is that the model design step is in principle straightforward: Suppose a process P is directly affected only by a substrate S and a modulator M. Then we know immediately that this process is represented as a function of the type (1) Here γ is a positive rate constant, and the exponents g1 and g2 are real-valued kinetic orders, the first of which is positive, because S is the substrate, and the second of which is negative if M is an inhibitor or positive if it is an activator. The magnitude

of each kinetic order reflects the strength of the effect of the variable, with which Inhibitors,research,lifescience,medical it is associated, on the process. In fact, if the modulator in Equation (1) has a negligible effect on P, its kinetic order g2 is close to 0, M raised to this number is close to 1, and the influence of M essentially Inhibitors,research,lifescience,medical disappears from the equation. In the case of heat stress in yeast, power-law functions may be used to represent the overall synthesis of transcripts as well as their degradation. To represent the specific case of a gene under the control of MSN, such as TPS1/2 or NTH1, the nuclear form of the Msn protein is included in the power-law

function for gene expression, because it exerts a positive, activating effect (see Figure 2). The dynamics of proteins are formulated in canonical Inhibitors,research,lifescience,medical models in a TKI-258 similar manner, namely through overall production and degradation terms. For example, the power-law term for protein synthesis is formulated to depend directly on the abundance of its corresponding transcript. As

a more complex example, Inhibitors,research,lifescience,medical but again of the same mathematical format, Equation (2) shows how different factors can be included in a power-law representation (see [28]). In this case, we model a reaction Inhibitors,research,lifescience,medical step Fi, in which the enzyme activity depends explicitly on the temperature in the milieu. As before, we include in the representation the substrates (Sj) and modulators (Mk), and account for their respective roles with kinetic orders hi,j and hmi,k. We also specify a rate constant αi and explicitly account for the amount of enzyme, Pi. If we are justified to assume a direct proportionality between enzyme amount and activity, its kinetic order is 1; otherwise a different, more appropriate kinetic order would be included. Finally, Qi is the direct effect of temperature (T) on this enzyme (with reference to 30 °C). It is Batimastat usually not included in metabolic models, but obviously becomes important for heat-stress studies. Therefore, the power-law formulation of the reaction step reads (2) Further details can be found in [28]. Thus, setting up a dynamic model in a symbolic canonical format is straightforward, because it is clear how different pieces of information are to be converted into components of the mathematical model. The real difficulties arise later, namely in the determination of appropriate parameter values, which are seldom known.